Review Article on Ion Pair Chromatography

[adam]

Hello

I was wondering if anyone knew of a good (reletively recent) review paper on the subject of ion pairing chromatography.

I thought I saw one mentioned on chromforum recently; but I just searched exhaustively and could not find it.

Any help would be much appreciated.

Thanks

[Noser222]

For that subject you might as well go with a book chapter.

[PHOBIUS]

Hello,
I am not sure if it helps, but I liked this paper a lot:
Uesugi et al., Journal of Chromatography B, 703 (1997) 63–74
It is not so recent. It is not even a review, but the mechanism of retention is nicely explained there.

[JGK]

Try "Ion Pairing - Blessing or Curse?" in February's issue of LC-GC North America

http://chromatographyonline.findpharma. ... oryId=9678

[Kostas Petritis]

Are you interested on the mechanism of ion-pairing chromatography or somekind of review on the different applications (or both)? For the mechanism there are some very nice fundamental papers (no equations or very little of them) but there are decades old.

[adam]

To reply to the last post, I am interested in a review of different applications.

One of the reasons I'm interested in this is that we sometimes have an API that does not have a chromophor, and I thought using a chromophoric ion pairing reagent may be one way to go.

Thanks

[Kostas Petritis]

Adam,

I see... You would actually be interested to do indirect detection of your API's that do not have a chromophor by using an ion pairing reagent that has a chromophor. There are several papers that were published on this in the late 80's and 90's but I haven't see anything lately (but haven't look for it either). Such an approach has it's drawbacks, one of them being the appearence of system peaks, and some limitations in terms of loading capacity and maybe dynamic range. It would be maybe more appropriate to use volatile ion-pairing reagents and ELSD or CLND or MS to detect your API's but I would look through my papers to find some references for you...

[juddc]

+1 for volatile IP agents. Perfluorinated carboxylic acids (TFA, Heptafluorobutyric acid, etc) work very nicely with ELSD, smaller ones equilibrate pretty quickly, may be used with shallow gradients if care is used (increase re-equilibration time), and don't appear to have any lasting effect on columns.

Remember that they can be used to move contaminant / excipient peaks as well as analytes, so even if your analyte isn't affected dramatically by the IP agent, your separation could be.

In recent months I've had two projects where this approach yielded really nice results.

[adam]

Someone out there must have used a chromophoric ion pair reagent to deal with a non-chromophoric analyte.

Anyone? Any thoughts?

[zokitano]

Someone out there must have used a chromophoric ion pair reagent to deal with a non-chromophoric analyte.

Anyone? Any thoughts?

I can recall now about one my earlier work on RP determination of phosphates and phosphites in API using inverse UV with tert-butylammonium hydroxide as pairing agent and potassium hydrogen phtalate additive in the mobile phase.

I should dig a little bit in my texts... If you're interested you can contact me via e-mail.

Regards

[mbicking]

Yes, the technique does work, but you would probably have to back to the late 70's and early 80's to find any references. The only reason it was originally used was because variable wavelength detectors were less common and less sensitive, RI detectors were worse than they are today, and ELSD hadn't been invented yet.

Having "no" chromaphore is probably not entirely accurate, unless the API is a simple inorganic. Even C-C and C-H bonds absorb, they just do so with small molar absorptivities and at short (i.e., < 210 nm) wavelengths. I would guess you could get enough sensitivity at 200-205 nm, and the results would be no worse than with indirect detection.

[Kostas Petritis]

Adam,

I have myself used ion-pairing chromatography and indirect (conductivity) detection in order to detect compounds without a chromophore (see Petritis et al J. Sep. Sci. 2001, 24, 397-405). Back then I digged all papers related to indirect detection, especially the ones that used ion-pair chromatography and a lot of papers relative to system peaks. I was really amazed of how the peaks in indirect detection can change direction (positive or negative peaks) depending on their net charge and elution relative to the main system peak (which retention time corresponding to the breakthrough of the adsorption isotherms of the ion pairing reagents).

I highly recommend reading the paper in order to see what potentially you are getting yourself into (although I was pretty happy with my findings and was able to find a pretty interesing application to apply the method).

Now the person that has worked a lot on the field (and who was one of the jury in my PhD thesis) is Jacque Crommen. Just search publications with his name and indirect as topic and you will find about 10 very useful publications on the subject (I will put them in my next post). One of the most useful in my opinion is in Journal of Chromatography, 461 (1989) 429-441. After a lot of equations there is a paragraph in the end entitled design of ion-pairing systems for indirect detection. I copy/paste the findings below...

Design of ion-pairing systems for indirect detection

From the basic expression for indirect detection in ion-pairing systems it follows that optimum sensitivity is obtained when the retention of the solute is close to that of the probe (a, close to 1) and when the detector response of the probe, e.g., the molar absorptivity is high. For solutes that are uncharged or have the same charge as that of the probe, the sensitivity increases with the fractional loading of the probe on the adsorbent, 8,. To avoid disturbances in sensitivity and peak shape, it is important to use mobile phases which contain only a few components: if possible only the probe and hydrophilic buffer. More than one hydrophobic component in the mobile phase may result in several retained system peaks and decrease the detection sensitivity for the components that are eluted between them. The probe should be aprotic to avoid detection disturbances due to protolysis. The buffer should have a capacity and concentration such that changes in the distribution of the probe are avoided.

[Kostas Petritis]

Here is some more reading for you:

1. Title: DETERMINATION OF MEPROBAMATE IN PHARMACEUTICAL DOSAGE FORMS ALSO CONTAINING CARBROMAL BY LIQUID-CHROMATOGRAPHY AND INDIRECT PHOTOMETRIC DETECTION
Author(s): BECHET, I; CECCATO, A; HUBERT, P, et al.
Source: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS Volume: 10 Issue: 10-12 Pages: 995-999 Published: OCT-DEC 1992
Times Cited: 4

2. Title: INDIRECT DETECTION IN REVERSED-PHASE LIQUID-CHROMATOGRAPHY - RESPONSE DEVIATIONS IN ION-PAIRING SYSTEMS
Author(s): ARVIDSSON, E; CROMMEN, J; SCHILL, G, et al.
Source: JOURNAL OF CHROMATOGRAPHY Volume: 461 Pages: 429-441 Published: JAN 6 1989
Times Cited: 32

3. Title: INDIRECT DETECTION IN REVERSED-PHASE LIQUID-CHROMATOGRAPHY - ION-PAIR RETENTION MODELS FOR ANIONIC ANALYTES AND MOBILE PHASE COMPONENTS ON POLYSTYRENE POLYMERS USING AN ALKALINE MOBILE PHASE
Author(s): ARVIDSSON, E; CROMMEN, J; SCHILL, G, et al.
Source: CHROMATOGRAPHIA Volume: 26 Pages: 45-52 Published: 1988
Times Cited: 6

4. Title: INDIRECT DETECTION IN LIQUID-CHROMATOGRAPHY .2. RESPONSE MODELS FOR REVERSED-PHASE NON-IONIC SYSTEMS
Author(s): CROMMEN, J; SCHILL, G; HERNE, P
Source: CHROMATOGRAPHIA Volume: 25 Issue: 5 Pages: 397-403 Published: MAY 1988
Times Cited: 37

5. Title: INDIRECT DETECTION IN REVERSED-PHASE LIQUID-CHROMATOGRAPHY - ION-PAIR RETENTION MODELS FOR CATIONS ON POLYSTYRENE POLYMERS
Author(s): ARVIDSSON, E; CROMMEN, J; SCHILL, G, et al.
Source: CHROMATOGRAPHIA Volume: 24 Pages: 460-468 Published: 1987
Times Cited: 28

6. Title: INDIRECT DETECTION IN LIQUID-CHROMATOGRAPHY .1. RESPONSE MODELS FOR REVERSED-PHASE ION-PAIRING SYSTEMS
Author(s): CROMMEN, J; SCHILL, G; WESTERLUND, D, et al.
Source: CHROMATOGRAPHIA Volume: 24 Pages: 252-260 Published: 1987
Times Cited: 64

7. Title: INDIRECT DETECTION IN HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY
Author(s): SCHILL, G; CROMMEN, J
Source: TRAC-TRENDS IN ANALYTICAL CHEMISTRY Volume: 6 Issue: 5 Pages: 111-116 Published: MAY 1987
Times Cited: 45

8. Title: INDIRECT UV DETECTION OF NON-IONIC SUBSTANCES IN LIQUID-CHROMATOGRAPHY BY ADDITION OF A UV-ABSORBING UNCHARGED COMPOUND TO THE MOBILE PHASE
Author(s): HERNE, P; RENSON, M; CROMMEN, J
Source: CHROMATOGRAPHIA Volume: 19 Pages: 274-279 Published: 1984
Times Cited: 25

9. Title: Indirect UV detection of hydrophilic ionized compounds in reversed-phase liquid chromatography by use of a UV-absorbing ion of the same charge.
Author(s): Crommen, J; Herne, P
Source: J Pharm Biomed Anal Volume: 2 Issue: 2 Pages: 241-53 Published: 1984

[adam]

Thanks Kostas. The info you provided is very helpful.

[Kostas Petritis]

Adam, you are wellcome,

Also, just out of the press this week, > 50 pages, about 500 references (covers what has been done in the last 10 years in IPC).

Title: Ion pairing chromatography
Author(s): Cecchi T
Source: CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY Volume: 38 Issue: 3 Pages: 161-213 Published: 2008